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Jian-Qiang Jiang,1,2,&ast; Jin-Tao Huang,1,&ast; Bin-Yan Zhong,1 Wei-Dong Wang,3,&ast; Jun-Hui Sun,4 Qi Wang,5 Wen-Bin Ding,6 Cai-Fang Ni,1 Xiao-Li Zhu1 1Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China; 2Department of Interventional Therapy, Nantong Tumor Hospital, Nantong, People’s Republic of China; 3Department of Interventional Radiology, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi, People’s Republic of China; 4Hepatobiliary and Pancreatic Interventional Treatment Center, Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 5Department of Interventional Radiology, Third Affiliated Hospital of Soochow University, Changzhou First Hospital, Changzhou, People’s Republic of China; 6Department of Interventional Radiology, Nantong First People’s Hospital, Nantong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiao-Li Zhu; Bin-Yan Zhong, Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, 188 Shizi St, Suzhou, 215006, People’s Republic of China, Tel/Fax +86 512 67972173, Email zhuxiaoli90@163.com; byzhongir@sina.comBackground and Objectives: This study aimed to evaluate the efficacy and safety of transarterial chemoembolization (TACE) in patients with unresectable early or intermediate hepatocellular carcinoma (HCC) and Child-Pugh (CP)-B liver dysfunction.Methods: This multicenter retrospective study enrolled patients with treatment-naïve HCC treated with TACE monotherapy between January 2012 and December 2020 at six Chinese hospitals. The primary outcome was overall survival (OS), and the secondary outcomes included the objective response rate (ORR) according to the modified RECIST and adverse events (AEs). Propensity score matching (PSM) was performed to reduce bias between the CP-B and CP-A groups.Results: A total of 847 patients were included in the study. CP-A patients had significantly longer OS (median, 22.0 vs 19.3 months, P = 0.032) than CP-B (score of 7– 9) patients, but a non-significant trend compared with CP-B (score of 7) patients (median, 22.0 vs 20.5 months, P = 0.254). After PSM, the median OS was 22.7 months for CP-A patients, while it was 19.3 months for CP-B (score of 7– 9) patients (p = 0.026) and 20.5 months for CP-B (score of 7) patients (p = 0.155). CP-A patients achieved a significantly better ORR (53.0% vs 35.8%, P < 0.05) compared to CP-B (score of 7– 9) patients, but a non-significant trend was observed in CP-B (score of 7) patients (53.0% vs 51.1%, P > 0.05). The post-embolization syndrome rates in the CP-A and CP-B (score of 7) cohorts were 52.1% and 53.3%, respectively. No new safety concerns were observed.Conclusion: Patients with HCC with a CP score of 7 receiving TACE showed a similar prognosis and safety profile to CP-A patients.Keywords: hepatocellular carcinoma, transarterial chemoembolization, Child-Pugh grade

This study is to evaluate the potential value of serum GP73 in ancillary cirrhosis diagnosis. 150 cirrhotic subjects and healthy subjects were retrospectively analyzed, and the two groups were compared in terms of Child‒Pugh grade. Serum GP73 was detected by enzyme-linked immunosorbent assay. Receiver operating characteristic curves were drawn to evaluate the diagnostic value of GP73, and the quantitative relationship between cirrhosis and GP73 was verified by logistic regression. The result showed in regard to serum biomarkers related to cirrhosis, the serum levels of GP73, TBIL, DBIL, and PT were higher and the ALB and PLT were lower in the cirrhosis group than in the control group (p = 0.000), and the area under the ROC curve of GP73 for diagnosing cirrhosis was 0.823 (p = 0.000), the cutoff value was 135 ng/ml, the sensitivity was 60.0%, and the specificity was 88.67%. Logistic regression analysis showed that GP73 > 135 ng/ml had an odds ratio of 11.735 (β= 2.463, 95% CI: 6.432-21.411, p = 0.000) for diagnosing cirrhosis. Additionally, the Child‒Pugh A, B, and C groups had different levels of GP73 (χ2 =17.840, p = 0.000). A pairwise comparison between the groups showed that there was a significant difference between grades A and B (p = 0.004) and between grades A and C (p = 0.002), but there was no significant difference between grades B and C (p = 1.000). We found serum GP73 levels were elevated in patients with cirrhosis. When the GP73 level was >135 ng/ml, the potential risk of a cirrhosis diagnosis increased approximately 12-fold. [ABSTRACT FROM AUTHOR]

Background: Immunotherapy plays an increasingly critical role in the systemic treatment of HCC. This current study aimed to establish a novel prognostic predictor of Programmed death 1 (PD-1) inhibitor therapy in hepatocellular carcinoma (HCC) independent of Child-Pugh grade. Methods: Our study screened patients with HCC who received PD-1 inhibitors at Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology from January 2018 to December 2020. ALG grade was determined by the patient's serum ALP and GGT levels before the initiation of PD-1 inhibitors. The endpoints of our study were overall survival (OS) and progression free survival (PFS). Follow-up ended at May 31, 2022. Results: Eighty-five patients (77 with Child-Pugh grade A, 8 with Child-Pugh grade B at baseline) were enrolled according to the inclusion criteria. Patients with Child-Pugh grade A achieved longer PFS and OS than those with Child-Pugh grade B. Patients with ALG grade 3 at baseline showed worse tumor response and poorer survival, and ALG grade could stratify patients with Child-Pugh grade A into subgroups with significantly different prognosis. Conclusions: ALG grade, combining ALP and GGT, is a novel and readily available prognostic marker and the predictive effect of ALG grade on patient prognosis is independent of Child-Pugh grade. [ABSTRACT FROM AUTHOR]

Background: Immunotherapy plays an increasingly critical role in the systemic treatment of HCC. This current study aimed to establish a novel prognostic predictor of Programmed death 1 (PD-1) inhibitor therapy in hepatocellular carcinoma (HCC) independent of Child-Pugh grade. Methods: Our study screened patients with HCC who received PD-1 inhibitors at Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology from January 2018 to December 2020. ALG grade was determined by the patient's serum ALP and GGT levels before the initiation of PD-1 inhibitors. The endpoints of our study were overall survival (OS) and progression free survival (PFS). Follow-up ended at May 31, 2022. Results: Eighty-five patients (77 with Child-Pugh grade A, 8 with Child-Pugh grade B at baseline) were enrolled according to the inclusion criteria. Patients with Child-Pugh grade A achieved longer PFS and OS than those with Child-Pugh grade B. Patients with ALG grade 3 at baseline showed worse tumor response and poorer survival, and ALG grade could stratify patients with Child-Pugh grade A into subgroups with significantly different prognosis. Conclusions: ALG grade, combining ALP and GGT, is a novel and readily available prognostic marker and the predictive effect of ALG grade on patient prognosis is independent of Child-Pugh grade. [ABSTRACT FROM AUTHOR]

Programmed death 1 (PD‐1) inhibitors are widely used for treatment of hepatocellular carcinoma (HCC). Hypothyroidism is commonly associated with this therapy, although the mechanism underlying this complication and effects on patient prognosis remain unclear. We retrospectively analysed the data of patients with HCC who received anti‐PD‐1 therapy at Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology between January 2018 and May 2020. Based on thyroid function evaluation, patients were categorised into hypothyroidism group and nonhypothyroidism group. Follow‐up was completed on February 28, 2021. The primary endpoint of our study was progression free survival (PFS). The study included 74 patients, and the disease control rate was higher in hypothyroidism group (62.7%, 27/43) than in nonhypothyroidism group (36.4%, 11/31) (P =.020). The PFS was longer in hypothyroidism group (7.44 months) than in nonhypothyroidism group (5.68 months) (P =.006). Additionally, the PFS of patients with hypothyroidism before immunotherapy (6.27 months) was also longer than that in nonhypothyroidism group (5.68 months), although the difference was statistically nonsignificant (P =.527). Cox regression analysis showed that the hazard ratios of hypothyroidism, Child‐Pugh grade B at initial admission and serum gamma‐glutamyl transferase levels >71 U/L before immunotherapy were 0.404 (95% confidence interval [CI]: 0.207‐0.791, P =.008), 2.753 (95%CI: 1.127‐6.455, P =.026) and 2.469 (95%CI: 1.155‐5.277, P =.020), respectively. Hypothyroidism was associated with prognosis in patients with HCC treated with PD‐1 inhibitors, and prognosis was more favourable in patients with hypothyroidism than in those without hypothyroidism. Hypothyroidism and the Child‐Pugh grade at initial admission were independently associated with patient prognosis. What's new? Several clinical studies have reported that immunotherapy‐induced thyroid dysfunction may be associated with better prognosis in patients with solid tumours. However, no study has explored the effect of hypothyroidism on the prognosis of hepatocellular carcinoma patients receiving PD‐1 inhibitors. In this retrospective study, patients with hepatocellular carcinoma who developed hypothyroidism during anti‐PD‐1 therapy showed better prognosis than those without hypothyroidism. Moreover, hypothyroidism and the Child‐Pugh grade at initial admission were independently associated with patient prognosis. Altogether, the results suggest that hypothyroidism is a predictor of enhanced antitumour effects by PD‐1 inhibitors in patients with hepatocellular carcinoma. [ABSTRACT FROM AUTHOR]

Background: The Albumin-Bilirubin (ALBI) score, widely used in predicting long-term prognosis for patients with hepatocellular carcinoma (HCC), has limitations due to serum albumin variability. This study aimed to develop and validate the Prealbumin-Bilirubin (preALBI) score as a reliable alternative., Methods: A multicenter cohort of HCC patients who underwent hepatectomy was randomly divided into the training and validation cohorts. The preALBI score was developed using Cox regression models within the training cohort, incorporating serum prealbumin and bilirubin levels as crucial determinants. The survival predictive accuracy was evaluated and compared between the preALBI score with two other staging systems, including the ALBI score and the Child-Pugh grade., Results: A total of 2409 patients were enrolled. In the training cohort, the preALBI score demonstrated superior performance in predicting long-term survival after hepatectomy. The preALBI score was associated with the best monotonicity of gradients (linear trend χ 2 : 72.84) and homogeneity (likelihood ratio χ 2 : 74.69), and the highest discriminatory ability (the areas under curves for 1-, 3-, and 5-year mortality: 0.663, 0.654, and 0.644, respectively). In addition, the preALBI was the most informative staging system in predicting survival (Akaike information criterion: 11325.65).The results remained consistent in both training and validation cohorts, indicating its reliable performance across different populations., Conclusion: The preALBI score, leveraging the stability of prealbumin, represents a promising tool for better patient stratification, providing more accurate prognostic predictions than the ALBI score and the Child-Pugh grade., Competing Interests: Declaration of competing interest We confirm that this work is original and has not previously been published. None of the authors have any financial disclosures or conflict of interest. Approval for this study was obtained from the Ethics Committee of the participating hospitals. All the authors have been involved in the design, performance, and interpretation of data of this study, and in drafting the article and its critical revision., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Abstract Background Underlying liver function is a major concern when applying surgical resection for hepatocellular carcinoma (HCC). We aimed to explore the capability of the albumin-bilirubin (ALBI) grade to predict post-hepatectomy liver failure (PHLF) and long-term survival after hepatectomy for HCC patients with different Barcelona Clinic Liver Cancer (BCLC) stages. Methods Between January 2010 and December 2014, 338 HCC patients who were treated with liver resection were enrolled. The predictive accuracy of ALBI grade system for PHLF and long-term survival across different BCLC stages was examined. Results A total of 26 (7.7%) patients developed PHLF. Patients were divided into BCLC 0/A and BCLC B/C categories. ALBI score was found to be a strong independent predictor of PHLF across different BCLC stages by multivariate analysis. In terms of overall survival (OS), it exhibited high discriminative power in the total cohort and in BCLC 0/A subgroup. However, differences in OS between ALBI grade 1 and 2 patients in BCLC B/C subgroup were not significant (P = 0.222). Conclusion The ALBI grade showed good predictive ability for PHLF in HCC patients across different BCLC stages. However, the ALBI grade was only a significant predictor of OS in BCLC stage 0/A patients and failed to predict OS in BCLC stage B/C patients.

Purpose: To find a subgroup that benefits most from transarterial chemoembolization (TACE) in terms of tumor number and size and liver profile in patients with intermediate-stage hepatocellular carcinoma (HCC). Materials and methods: Data of 325 intermediate-stage HCC patients who received TACE as the initial treatment were gathered. Four tumor numbers (3-6 tumors) and five maximum tumor diameters (3-7 cm) as well as all of their combinations but one (3 tumors and 3 cm) and Child-Pugh grade were used as variables to ascertain prognostic factors. Results: The respective 1-, 3-, and 5-year overall survival rates in all patients were 86.5, 47.0, and 23.7 %, respectively. Tumor numbers of 4 ( P = 0.00145) and 5 ( P = 0.036), and tumor size of 7 cm ( P = 0.015), and 12 other combinations of tumor number and size, and Child-Pugh grade ( P = 0.0015) were identified as significant prognostic factors in univariate analysis, and 4 tumors of 7 cm ( P = 0.0008) and Child-Pugh grade ( P = 0.0036) remained significant in the stepwise Cox proportional hazard model. The overall survival was significantly better in a patient subgroup having two factors other than patient subgroups having one or no prognostic factors. Conclusion: A patient subgroup having two prognostic factors benefited most from TACE in intermediate-stage HCC patients. [ABSTRACT FROM AUTHOR]

Background: Thermal ablation is one of the first-line treatments for patients with hepatocellular carcinoma (HCC) with a massive potential of long-term cure. However, it is disadvantaged by the relatively high rate of postoperative recurrence. In this study, a comparison was performed in the prognostic performance between albumin-bilirubin (ALBI) grade and Child-Pugh (C-P) grade for those HCC patients undergoing thermal ablation., Methods: A total of 467 patients undergoing thermal ablation as the initial therapy were recruited and retrospectively analyzed. Then, an investigation was carried out into the prognostic values of overall survival (OS) and recurrence free survival (RFS) through ALBI grade and C-P score, separately. Besides, propensity-score matching (PSM) was performed to adjust the significantly different patient characteristics for ALBI grade based on C-P A patients., Results: In the multivariate analysis, both ALBI and C-P grades were treated as independent prognostic factors for OS. Cox multivariate analysis was conducted to reveal that the independent risk factors for postoperative HCC recurrence included ALBI grade 2-3, multiple tumors, tumor size ≥2 cm, and age ≥65 years. Following PSM (1:1), both ALBI-1 and ALBI-2 groups were found to be well matched in all of the parameters involved. Depending on the ALBI grade (113 ALBI-1 vs. 113 ALBI-2), C-P A patients were reclassified into two risk groups for OS (P=0.0058) and RFS (P=0.012), respectively., Conclusions: The conventional C-P classification, despite its necessity, is less effective in assessing preoperative liver dysfunction for HCC patients and subjected to some limitations. Characterized by simplicity and objectivity, the ALBI grade has demonstrated its greater prognostic value than C-P grade for HCC patients who underwent thermal ablation., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tcr.amegroups.com/article/view/10.21037/tcr-22-244/coif). The authors have no conflicts of interest to declare., (2022 Translational Cancer Research. All rights reserved.)

Précised liver reserve function estimation is of great significance for predicting the survival time, post-hepatectomy liver failure and individualized comprehensive treatment strategies in hepatocellular carcinoma (HCC) patients. Currently, the widely used Child-Pugh (CP) classification and indocyanine green 15-minute retention rate (ICGR 15) have certain flaws and limitations. The albumin-bilirubin (ALBI) grading especially makes up for the deficiency of CP classification, and can provide an objective, simple, accurate and evidence-based method to estimate and guide the liver reserve function of HCC patients. This paper follows up and summarizes the research progress of ALBI grading estimation at home and abroad on liver reserve function of HCC patients.

Transarterial chemoembolization (TACE) is the recommended first-line treatment for intermediate-stage hepatocellular carcinoma (HCC). In patients who became refractory to TACE, a treatment switch to tyrosine kinase inhibitors (TKIs) needs to be considered. However, TACE could worsen liver function, thereby narrowing the time window for a switch to TKIs because TKIs are recommended for patients with Child-Pugh grade A (CP-A). We investigated the factors associated with CP grade deterioration after TACE. Among patients who underwent TACE, 125 patients with CP-A were enrolled. The cumulative CP grade deterioration rates were 20.3%, 27.1%, and 41.4% at six months, one year, and two years, respectively. Multivariate analysis revealed that factors associated with CP grade deterioration included high Mac-2 binding protein glycosylation isomer (M2BPGi) levels (>2.00 cut-off index) and beyond the up-to-seven criteria. The cumulative CP grade deterioration rates of patients with high M2BPGi and beyond the up-to-seven criteria were 50.6% and 59.2% at six months and one year, respectively, which were significantly higher than for those in any other groups. The combination of M2BPGi and up-to-seven criteria could be a surrogate marker for predicting CP grade deterioration after TACE. In patients with intermediate-stage HCC, elevated M2BPGi levels, and beyond the up-to-seven criteria, an early treatment switch to TKIs should be considered to improve their prognosis. [ABSTRACT FROM AUTHOR]

Background: Underlying liver function is a major concern when applying surgical resection for hepatocellular carcinoma (HCC). We aimed to explore the capability of the albumin-bilirubin (ALBI) grade to predict post-hepatectomy liver failure (PHLF) and long-term survival after hepatectomy for HCC patients with different Barcelona Clinic Liver Cancer (BCLC) stages. Methods: Between January 2010 and December 2014, 338 HCC patients who were treated with liver resection were enrolled. The predictive accuracy of ALBI grade system for PHLF and long-term survival across different BCLC stages was examined. Results: A total of 26 (7.7%) patients developed PHLF. Patients were divided into BCLC 0/A and BCLC B/C categories. ALBI score was found to be a strong independent predictor of PHLF across different BCLC stages by multivariate analysis. In terms of overall survival (OS), it exhibited high discriminative power in the total cohort and in BCLC 0/A subgroup. However, differences in OS between ALBI grade 1 and 2 patients in BCLC B/C subgroup were not significant (P = 0.222). Conclusion: The ALBI grade showed good predictive ability for PHLF in HCC patients across different BCLC stages. However, the ALBI grade was only a significant predictor of OS in BCLC stage 0/A patients and failed to predict OS in BCLC stage B/C patients. [ABSTRACT FROM AUTHOR]

Background and Study Aims: To investigate the relationship among fibrotic, haemostatic and endotoxic changes in patients with different degrees of liver cirrhosis., Patients and Methods: Liver fibrotic markers, including hyaluronic acid (HA), Ccollagen IV (Col-IV), laminin (LN), and N-terminal pro-peptide of collagen type III (PIIINP), were determined by radioimmunoassay. A series of haemostatic tests, including prothrombin time (PT), international normalized ratio, activated partial thromboplastin time, antithrombin-III, thrombin time, fibrinogen, fibrin(ogen) degradation product and D-dimer were determined using an automatic coagulation analyszer. Plasma levels of endotoxin were detected quantitatively using an endotoxin detection kit. Correlation analysis of the data was performed., Results: Based on Child-Pugh classification, statistically significant differences in fibrotic markers and haemostatic parameters were found in 249 patients with liver cirrhosis, while no significant differences in endotoxin levels were observed. Based on ascites classification, statistically significant differences in fibrotic markers (such as HA, Col-IV and PIIINP, except for LN) and haemostatic parameters were found. As for endotoxin levels, there were significant differences between the ascites, spontaneous bacterial peritonitis (SBP) and no-ascites groups, while no significant differences were observed between the ascites and SBP groups. Correlation analysis demonstrated some correlation among fibrotic markers, haemostatic parameters and endotoxin., Conclusions: A close relationship exists between the severity of cirrhosis and fibrotic changes, as well as haemostatic changes. Endotoxin may be an important contributing factor to the development of ascites in cirrhosis. Some correlation may exist between fibrosis, haemostatic and endotoxin.

Background: The prognostic performance of the albumin-bilirubin (ALBI) grade in hepatocellular carcinoma (HCC) as an objective method of assessing liver function was investigated., Methods: Data from 2099 patients with HCC in Korea were collected and analyzed retrospectively. The discriminative performance of ALBI grade was compared with Child-Pugh (C-P) grade for different stages or treatments., Results: The median follow up duration was 16.2 months (range: 1.0-124.9). The median survival times were 49.7 months for C-P grade A (65.8%), 12.4 months for C-P grade B (25.5%), and 4.2 months for C-P grade C (8.6%) (P < 0.001). The median survival times were 84.2 months for ALBI grade 1 (32.8%), 25.5 months for ALBI grade 2 (53.5%), and 7.7 months for ALBI grade 3 (13.7%) (P < 0.001). In early UICC stages, ALBI grade showed better discriminative performance than C-P grade. In curative treatments, ALBI grade also showed better discriminative performance than C-P grade (Harrell's C: 0.624 (C-P grade) vs 0.667 [ALBI grade])., Conclusions: ALBI grade provided better prognostic performance in survival analysis and better distribution of the grades than C-P grade in HCC, suggesting that ALBI grade could be a good alternative grading system for liver function in patients with HCC., (© 2018 Wiley Periodicals, Inc.)

The therapeutic strategy against hepatocellular carcinoma (HCC) is determined by tumor stage and liver function. Improvements of stratification contribute to extending the survival of patients. However, stratification has been attributed little attention in animal models largely due to the lack of suitable models. Herein we showed that the recently-reported, non-alcoholic steatohepatitis-derived HCC model (STAM model) is the first murine model in which the concept of human stratification is applicable by demonstrating the following features: (i) at least 4 detectable tumor nodules; (ii) average tumor growth rate of 150 % from 16 to 20 weeks of age; (iii) no visible metastasis; and (iv) relatively preserved liver function. These observations suggested that HCC in STAM mice is equivalent to stages B to C of the Barcelona Clinic Liver Cancer (BCLC) staging system for humans. Application of the stratification concept to experimental animals will create new avenues to establish pharmacological intervention against HCC., (Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)